Medicalgenomics.org : an open source database and retrieval system for biomedical analysis

Die Molekularbiologie von Menschen ist ein hochkomplexes und vielfältiges Themengebiet, in dem in vielen Bereichen geforscht wird. Der Fokus liegt hier insbesondere auf den Bereichen der Genomik, Proteomik, Transkriptomik und Metabolomik, und Jahre der Forschung haben große Mengen an wertvollen Daten zusammengetragen. Diese Ansammlung wächst stetig und auch für die Zukunft ist keine Stagnation absehbar. Mittlerweile aber hat diese permanente Informationsflut wertvolles Wissen in unüberschaubaren, digitalen Datenbergen begraben und das Sammeln von forschungsspezifischen und zuverlässigen Informationen zu einer großen Herausforderung werden lassen. Die in dieser Dissertation präsentierte Arbeit hat ein umfassendes Kompendium von humanen Geweben für biomedizinische Analysen generiert. Es trägt den Namen medicalgenomics.org und hat diverse biomedizinische Probleme auf der Suche nach spezifischem Wissen in zahlreichen Datenbanken gelöst. Das Kompendium ist das erste seiner Art und sein gewonnenes Wissen wird Wissenschaftlern helfen, einen besseren systematischen Überblick über spezifische Gene oder funktionaler Profile, mit Sicht auf Regulation sowie pathologische und physiologische Bedingungen, zu bekommen. Darüber hinaus ermöglichen verschiedene Abfragemethoden eine effiziente Analyse von signalgebenden Ereignissen, metabolischen Stoffwechselwegen sowie das Studieren der Gene auf der Expressionsebene. Die gesamte Vielfalt dieser Abfrageoptionen ermöglicht den Wissenschaftlern hoch spezialisierte, genetische Straßenkarten zu erstellen, mit deren Hilfe zukünftige Experimente genauer geplant werden können. Infolgedessen können wertvolle Ressourcen und Zeit eingespart werden, bei steigenden Erfolgsaussichten. Des Weiteren kann das umfassende Wissen des Kompendiums genutzt werden, um biomedizinische Hypothesen zu generieren und zu überprüfen.

Migrazione concorrente di macchine virtuali su piattaforme open source

Questa tesi si pone l’obiettivo di effettuare un’analisi aggiornata sulla recente evoluzione del Cloud Computing e dei nuovi modelli architetturali a sostegno della continua crescita di richiesta di risorse di computazione, di storage e di rete all'interno dei data center, per poi dedicarsi ad una fase sperimentale di migrazioni live singole e concorrenti di macchine virtuali, studiandone le prestazioni a livello di risorse applicative e di rete all’interno della piattaforma open source di virtualizzazione QEMU-KVM, oggi alla base di sistemi cloud-based come Openstack. Nel primo capitolo, viene effettuato uno studio dello stato dell’arte del Cloud Computing, dei suoi attuali limiti e delle prospettive offerte da un modello di Cloud Federation nel futuro immediato. Nel secondo capitolo vengono discusse nel dettaglio le tecniche di live migration, di recente riferimento per la comunità scientifica internazionale e le possibili ottimizzazioni in scenari inter e intra data center, con l’intento di definire la base teorica per lo studio approfondito dell’implementazione effettiva del processo di migrazione su piattaforma QEMU-KVM, che viene affrontato nel terzo capitolo. In particolare, in quest’ultimo sono descritti i principi architetturali e di funzionamento dell'hypervisor e viene definito il modello di progettazione e l’algoritmo alla base del processo di migrazione. Nel quarto capitolo, infine, si presenta il lavoro svolto, le scelte configurative e progettuali per la creazione di un ambiente di testbed adatto allo studio di sessioni di live migration concorrenti e vengono discussi i risultati delle misure di performance e del comportamento del sistema, tramite le sperimentazioni effettuate.

Analisi delle prestazioni di un codice di calcolo open-source per l'elaborazione dati GNSS in modalità cinematica finalizzata al monitoraggio di strutture e applicazione di filtri sequenziali

Il presente lavoro di tesi si pone come obbiettivo l’elaborazione di dati GNSS in modalità cinematica post-processing per il monitoraggio strutturale e, in una seconda fase, lo studio delle precisioni raggiungibili delle soluzioni ottenute utilizzando algoritmi di post-elaborazione del dato. L’oggetto di studio è la torre Garisenda, situata in piazza Ravegnana, accanto alla torre Asinelli, nel centro storico di Bologna, da tempo oggetto di studi e monitoraggi per via della sua inclinazione particolarmente critica. Per lo studio è stato utilizzato un data set di quindici giorni, dal 15/12/2013 al 29/12/2013 compresi. Per l’elaborazione dei dati è stato utilizzato un software open source realizzato da ricercatori del Politecnico di Milano, goGPS. Quest'ultimo, essendo un codice nuovo, è stato necessario testarlo al fine di poter ottenere dei risultati validi. Nella prima fase della tesi si è quindi affrontato l’aspetto della calibrazione dei parametri che forniscono le soluzioni più precise per le finalità di monitoraggio considerando le possibili scelte offerte dal codice goGPS. In particolare sono stati imposti dei movimenti calibrati e si è osservata la soluzione al variare dei parametri selezionati scegliendo poi quella migliore, ossia il miglior compromesso tra la capacità di individuare i movimenti e il rumore della serie. Nella seconda fase, allo scopo di poter migliorare le precisioni delle soluzioni si sono valutati metodi di correzione delle soluzioni basati sull'uso di filtri sequenziali e sono state condotte analisi sull'incremento di precisione derivante dall'applicazione di tali correzioni.

Detrusor activity is impaired during thoracic epidural analgesia after open renal surgery

There are no data on lower urinary tract function during postoperative thoracic epidural analgesia (TEA). Because selected segmental blockade can be achieved with epidural analgesia, we hypothesized that lower urinary tract function remains unchanged during TEA within segments T4-T11 after open renal surgery.

Toward optimal display of physiologic status in critical care: I. Recreating bedside displays from archived physiologic data

BACKGROUND: Physiologic data display is essential to decision making in critical care. Current displays echo first-generation hemodynamic monitors dating to the 1970s and have not kept pace with new insights into physiology or the needs of clinicians who must make progressively more complex decisions about their patients. The effectiveness of any redesign must be tested before deployment. Tools that compare current displays with novel presentations of processed physiologic data are required. Regenerating conventional physiologic displays from archived physiologic data is an essential first step. OBJECTIVES: The purposes of the study were to (1) describe the SSSI (single sensor single indicator) paradigm that is currently used for physiologic signal displays, (2) identify and discuss possible extensions and enhancements of the SSSI paradigm, and (3) develop a general approach and a software prototype to construct such "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator (MWA) framework-a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA) scripts aimed to create dynamic visualizations (eg, video files in AVI format) of patient vital signs recorded from bedside (intensive care unit or operating room) monitors. Multi Wave Animator creates animations in which vital signs are displayed to mimic their appearance on current bedside monitors. The source code of MWA is freely available online together with a detailed tutorial and sample data sets.

Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development

Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database. 48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit.

Investigation of a unique short open reading frame within the 3' untranslated region of the canine distemper virus matrix messenger RNA

Increasing evidence suggest that the long "untranslated" region (UTR) between the matrix (M) and the fusion (F) proteins of morbilliviruses has a functional role. In canine distemper virus (CDV), the F 5' UTR was recently shown to code for a long F signal peptide (Fsp). Subsequently, it was reported that the M/F UTRs combined with the long Fsp were synergistically regulating the F mRNA and protein expression, thereby modulating virulence. Unique to CDV, a short putative open reading frame (ORF) has been identified within the wild-type CDV-M 3' UTR (termed M2). Here, we investigated whether M2 was expressed from the genome of the virulent and demyelinating A75/17-CDV strain. An expression plasmid encoding the M2 ORF tagged both at its N-terminal (HA) and C-terminal domains (RFP), was first constructed. Then, a recombinant virus with its putative M2 ORF replaced by HA-M2-RFP was successfully recovered from cDNA (termed recA75/17(green)-HA-M2-RFP). M2 expression in cells transfected or infected with these mutants was studied by immunoprecipitation, immunofluorescence, immunoblot and flow cytometry analyses. Although fluorescence was readily detected in HA-M2-RFP-transfected cells, absence of red fluorescence emission in several recA75/17(green)-HA-M2-RFP-infected cell types suggested lack of M2 biosynthesis, which was confirmed by the other techniques. Consistent with these data, no functional role of the short polypeptide was revealed by infecting various cell types with HA-M2-RFP over-expressing or M2-knockout recombinant viruses. Thus, in sharp contrast to the CDV-F 5' UTR reported to translate a long Fsp, our data provided evidence that the CDV-M 3' UTR does not express any polypeptides.

Government Influence and the Failure of Fannie Mae and Freddie Mac

In 2008 two government-sponsored enterprises, Fannie Mae and Freddie Mac, were placed into conservatorship due to insolvency. The financial bailout of the two publically traded corporations came at the expense of the American tax payer. This study investigates the relationship between direct and indirect government influence and the increasing risk taking of Fannie Mae and Freddie Mac from the late 1990’s through their conservatorship in 2008. As government-sponsored enterprises Fannie Mae and Freddie Mac have many special advantages that other publically traded companies did not possess. These advantages allowed Fannie Mae and Freddie Mac to increase their profitability. Theoretical literature regarding Congress and the bureaucracy suggests that the actions of bureaucrats can be linked to the preferences of Congressional members because bureaucrats are responsive to potential threats or perceived threats from the legislature. This theory is applicable to Fannie Mae and Freddie Mac, and is used to explain why the government was able to directly and indirectly influence the government-sponsored enterprises. Overall this investigation has determined that the United States government pursued a clear mission that determined to increase the availability of housing to all Americans, specifically to low-income and under-served individuals, through the use of the government-sponsored enterprises. Despite this link there is no conclusive data to show that the pursuit of this housing mission led Fannie Mae and Freddie Mac to operate in riskier business segments. This study has also found that motivation regarding profit-seeking and compensation structure provide a more plausible explanation for why the government-sponsored enterprises began to engage in riskier business practices that led to their insolvency.

Studying the Roles of Nonprofits, Government, and Business in Providing Activities and Services to Youth in the Phoenix Metropolitan Area

The article addresses the questions, What do children in urban areas do on Saturdays? What types of organizational resources do they have access to? Does this vary by social class? Using diary data on children's activities on Saturdays in the Phoenix-Mesa-Scottsdale metropolitan area, the authors describe the different types of venues (households, businesses, public space, associations, charities, congregations, and government/tribal agencies) that served different types of children. They find that the likelihood of using a charity or business rather than a government or tribal provider increased with family income. Also, the likelihood of using a congregation or a government facility rather than a business, charity, or household increased with being Hispanic. The authors discuss the implications for the urban division of labor on Saturdays and offer research questions that need further investigation.

“All Data is Credit Data,” or, On Close Reading as a Reciprocal Process in Digital Knowledge Environments

The new knowledge environments of the digital age are oen described as places where we are all closely read, with our buying habits, location, and identities available to advertisers, online merchants, the government, and others through our use of the Internet. This is represented as a loss of privacy in which these entities learn about our activities and desires, using means that were unavailable in the pre-digital era. This article argues that the reciprocal nature of digital networks means 1) that the privacy issues that we face online are not radically different from those of the pre-Internet era, and 2) that we need to reconceive of close reading as an activity of which both humans and computer algorithms are capable.

Talents in Migration Processes in the Conditions of the Czech Republic of the Nineties

The transformation of the 1990s has had a bearing on the academic and scientific world, as is becoming increasingly obvious with the changing numbers of foreign students wishing to study in the Czech Republic and of Czech students wishing to study abroad, the virtual collapse of doctoral studies, and the rapidly increasing age of Czech academics (placed at 48 by official sources and at rather more by this research). At the same time there is an apparent lack of interest in analysing and understanding these trends, which Mr. Cermak terms an ostrich policy, although his research showed that academics are in fact both aware and concerned about them. The mid-1990s migration of talent to and from R+D in the Czech Republic is also reflected in the number of talented Czech students studying abroad, who represent the largest and most interesting group of actual and potential migrants. Mr. Cermak's study took the form of a Delphi enquiry participated in by 44 specialists, including experts in the problems of higher education and science policy from the Presidium of the Higher Education Council (n = 23), members of the Council's Science and Research Commission (n = 14), former and current managers of higher education authorities (n = 4) and selected participants of the longitudinal talent research (n = 3). Questions considered included the influence of continuing talent migration from domestic R+D on the efficiency of domestic higher education, the diversification of forms of the brain drain and their impact on other processes in society, the possibility of positive influence on the brain drain processes to minimise the risks it presents, and the use of the knowledge obtained about the brain drain. The study revealed a clear drop of interest in brain drain problems in higher education in the mid-1990s, which is probably related to the collapsed of Czech R+D in the field of talent education. The effects on this segment of the labour market appeared earlier, with a major migration wave in 1991-1993 which significantly "cleared" the area of scientific talent. In addition, prospective talents from the ranks of younger students have not been integrated into domestic R+D, leading to the increasing average age of those working in this field. "Talent scouting" tended to be oriented towards much younger individuals, even in some cases towards undergraduate students. The R+D institutions deprived of human resources considered as basic in a functional R+D system have lost much of their dynamism and so no longer attract not only domestic talent but also talent from other regions. As a result the public, including the mass media and political structures, have stopped regarding the support of domestic science as a priority. This is clear both among the young people who are important for the future development of R+D (support for the education of talented children has dropped), from the drop in the prestige of this area as a profession among university students, and from the lack of explicit support for R+D by any of the political parties. On the basis of his findings Mr. Cermak concludes that there is no basis for the belief that the brain drain will represent a positive force in stimulating the development of the open society. Migration data shows that the outflow of talent from the Czech Republic far exceeds the inflow, and that the latter is largely short-term. Not only has the number of returning Czech professors dropped to half of its level at the beginning of the 1990s, but they also tend to take up only short-term contracts and retain their foreign positions. Recruitment of scientific talent from other countries, including the Slovak Republic, is limited. Furthermore internal contacts between those already involved in R+D have been badly hit by economic pressures and institutional co-operation has dropped to a minimum. There have been few moves to counteract this situation, the only notable one being the Program 250, launched in 1996 with government support to try and attract younger (i.e. under 40) talent into R+D. Its resources are however limited and its effects have not so far been evaluated. The deficit of academic and scientific talent in the Czech Republic is increasing and two major directions of academic work are emerging. Classic higher education science based on the teaching process is declining, largely due to economic factors, while there is an increasing emphasis on special; ad hoc projects which cannot be related directly to teaching but are often interesting to specialists outside the Czech Republic. This is shown clearly by the increase in publishing and in participation in domestic and foreign grant projects, which often serve to supplement the otherwise low salaries in the higher education sector. This tend was also accelerated by the collapse of applied R+D in individual sectors of the national economy and by substantial cutbacks in the Czech Academy of Sciences, which formerly fostered such research. Some part of the output of this research can be used in the education system and its financial contribution does significantly affect the stability of the present staff, but Mr. Cermak sees it as generally unfavourable for the development of talent education. In addition, it has led to a certain resignation on the question of integration into international structures, due to the emphasis on short-term targets, commercial advantages and individualism rather than team work. At the same time, he admits that these developments reflect those in other areas of the transformation in the Czech Republic.

Activated coagulation during open and endovascular abdominal aortic aneurysm repair

OBJECTIVE: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR). METHODS: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected. RESULTS: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution. CONCLUSION: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.

"From Dartboards to Dashboards: The Imperative of using Data to Improve Student Achievement"

Aimee Guidera, Director of the National Data Quality Campaign, delivered the second annual Lee Gurel '48 Lecture in Education, "From Dartboards to Dashboards: The Imperative of Using Data to Improve Student Outcomes." Aimee Rogstad Guidera is the Founding Executive Director of the Data Quality Campaign. She manages a growing partnership among national organizations collaborating to improve the quality, accessibility and use of education data to improve student achievement. Working with 10 Founding Partners, Aimee launched the DQC in 2005 with the goal of every state having a robust longitudinal data system in place by 2009. The Campaign is now in the midst of its second phase focusing on State Actions to ensure effective data use. Aimee joined the National Center for Educational Accountability as Director of the Washington, DC office in 2003. During her eight previous years in various roles at the National Alliance of Business, Aimee supported the corporate community's efforts to increase achievement at all levels of learning. As NAB Vice President of Programs, she managed the Business Coalition Network, comprised of over 1,000 business led coalitions focused on improving education in communities across the country. Prior to joining the Alliance, Aimee focused on school readiness, academic standards, education goals and accountability systems while in the Center for Best Practices at the National Governors Association. She taught for the Japanese Ministry of Education in five Hiroshima high schools where she interviewed educators and studied the Japanese education system immediately after receiving her AB from Princeton University’s Woodrow Wilson School of Public & International Affairs. Aimee also holds a Masters Degree in Public Policy from Harvard’s John F. Kennedy School of Government.

Physicians' philosophy of care: a comparison of complementary and conventional medicine

BACKGROUND: This project is part of an evaluation of complementary and alternative medicine (CAM) aimed at providing a scientific basis for the Swiss Government to include 5 CAM methods in basic health coverage: anthroposophic medicine, homeopathy, neural therapy, phytotherapy and Traditional Chinese Medicine (TCM). OBJECTIVES: The objective was to explore the philosophy of care (convictions and values, priorities in medical activity, motivation for CAM, criteria for the practice of CAM, limits of the used methods) of conventional and CAM general practitioners (GPs) and to determine differences between both groups. MATERIALS AND METHODS: This study was a cross-sectional survey of a representative sample of 623 GPs who provide complementary or conventional primary care. A mailed questionnaire with open-ended questions focusing on the philosophy of care was used for data collection. An appropriate methodology using a combination of quantitative and qualitative approaches was developed. RESULTS: Significant differences between both groups include philosophy of care (holistic versus positivistic approaches), motivation for CAM (intrinsic versus extrinsic) and priorities in medical activity. Both groups seem to be aware of limitations of the therapeutic methods used. The study reveals that conventional physicians are also using complementary medicine. DISCUSSION: Our study provides a wealth of data documenting several aspects of physicians' philosophy of care as well as differences and similarities between conventional and complementary care. Implications of the study with regard to quality of care as well as ethical and health policy issues should be investigated further.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.